Blood flow control in a blood treatment device

ABSTRACT

A first flow path is defined within a first panel that forms a part of an extracorporeal fluid circuit. A second flow path is defined within a second panel that also forms a part of the extracorporeal fluid circuit. The first and second panels are oriented in a fluid processing cartridge for mounting as an integrated unit on a fluid processing machine and for removal as an integrated unit from the fluid processing machine.

RELATED APPLICATIONS

This application is a continuation-in-part of co-pending U.S. patentapplication Ser. No. 08/800,881, filed Feb. 14, 1997, and entitled“Hemofiltration System,” which is incorporated herein by reference. Thisapplication is also a divisional of co-pending U.S. patent applicationSer. No. 09/451,238, filed Nov. 29, 1999, and entitled “Systems andMethods for Performing Frequent Hemofiltration,” which is incorporatedherein by reference.

FIELD OF THE INVENTION

This invention relates to systems and methods for processing blood,e.g., for filtration, pheresis, or other diagnostic or therapeuticpurposes.

BACKGROUND OF THE INVENTION

There are many types of continuous and intermittent blood processingsystems, each providing different therapeutic effects and demandingdifferent processing criteria.

For example, hemofiltration emulates normal kidney activities for anindividual whose renal function is impaired or lacking. Duringhemofiltration, blood from the individual is conveyed in anextracorporeal path along a semipermeable membrane, across which apressure difference (called transmembrane pressure) exists. The pores ofthe membrane have a molecular weight cut-off that can thereby passliquid and uremic toxins carried in blood. However, the membrane porescan not pass formed cellular blood elements and plasma proteins. Thesecomponents are retained and returned to the individual with thetoxin-depleted blood. Membranes indicated for hemofiltration arecommercially available and can be acquired from, e.g., Asahi Medical Co.(Oita, Japan).

After hemofiltration, fresh physiologic fluid is supplied totoxin-depleted blood. This fluid, called replacement fluid, is bufferedeither with bicarbonate, lactate, or acetate. The replacement fluidrestores, at least partially, a normal physiologic fluid andelectrolytic balance to the blood. Usually, an ultrafiltration functionis also performed during hemofiltration, by which liquid is replaced inan amount slightly less than that removed. Ultrafiltration decreases theoverall fluid level of the individual, which typically increases, in theabsence of ultrafiltration, due to normal fluid intake between treatmentsessions.

Following hemofiltration, fluid balancing, and ultrafiltration, theblood is returned to the individual.

SUMMARY OF THE INVENTION

One aspect of the invention provides a fluid processing systemcomprising an extracorporeal circuit for circulating a fluid from anindividual through a filter to remove waste and to return fluid to theindividual after removal of waste. A first portion of the extracorporealcircuit is integrated, at least in part, within a first panel. A secondportion of the extracorporeal circuit is integrated, at least in part,within a second panel. The system further includes a fluid processingcartridge, which orients the first and second panels for mounting as anintegrated unit on a fluid processing machine and for removal as anintegrated unit from the fluid processing machine.

In one embodiment, the first portion of the extracoporeal circuithandles waste fluid, and the second portion of the extracoporeal circuithandles replacement fluid for return to the individual.

In one embodiment, the first and second portions of the extracorporealcircuit include in-line chambers that volumetrically balance waste fluidremoved from the individual and waste replacement fluid returned to theindividual. The in-line chambers can occupy a fixed volume cavity on thefluid processing machine, whereby the in-line chambers possess a volumedefined by the fixed volume cavity on the machine.

In one embodiment, at least one of the first and second panels includesan operative region that flexes in response to an external force appliedby the fluid processing machine. The operative region can comprise,e.g., an in-line clamping region that flexes to occlude fluid flow, oran in-line pump tube that flexes in response to peristaltic force topump fluid, or an operative region that permits sensing of a flowcondition by a sensor on the fluid processing machine.

In one embodiment, the fluid processing cartridge includes a traycontaining the first and second panels, which are oriented within thetray in an overlaying relationship.

Another aspect of the invention provides a blood processing system. Thesystem comprises an extracoporeal fluid circuit. The circuit includes afirst flexible panel having a pattern of seals defining a first flowpath that forms a part of the extracorporeal fluid circuit. The circuitalso includes a second flexible panel having a pattern of seals defininga second flow path that forms another part of the extracorporeal fluidcircuit. A fluid processing cartridge retains the first and secondflexible panels in an overlaying relationship. The system furtherincludes a fluid processing device including a chassis to removablymount the fluid processing cartridge with the first flexible paneloriented adjacent to the chassis. The fluid processing device includesan actuator on the chassis operating to apply force through the firstflexible panel to a region of the second flexible panel to either pumpfluid in the second flow path or occlude flow in the second flow path.

The actuator can comprise, e.g. a pump element to apply a peristalticforce to the region of the second flexible panel through the firstflexible panel, or an in-line pump tube to which the peristaltic forceis applied, or a clamp element to apply an occlusion force to the regionof the second flexible panel through the first flexible panel.

In one embodiment, a sensor on the chassis senses a flow condition inthe second flow path through the first and second flexible panels.

In one embodiment, the fluid processing cartridge includes a traymovable into and out of association with the chassis. In onearrangement, the tray includes a cut-out exposing a region of the firstflexible panel to the actuator.

Another aspect of the invention provides a hemofiltration machine. Themachine includes a chassis and an operating element on the chassiscomprising at least one of a peristaltic pump, a clamp, and a sensor. Adoor is movable with respect to the chassis between a first positionenabling mounting of a fluid processing cartridge on the chassis and asecond position holding the fluid processing cartridge on the chassis ina predetermined orientation with the operating element.

In one embodiment, the door moves in a path toward and away from thechassis.

In one embodiment, a depression on the chassis defines a space of knownvolume to accommodate a fluid balancing chamber carried in the fluidprocessing cartridge.

In one embodiment, the door includes at least one pump race for registrywith a pump region carried in the fluid processing cartridge.

Another aspect of the invention provides a fluid processing method. Themethod establishes an extracoporeal fluid circuit that communicates witha filter. The method defines within a first panel a first flow path thatforms a part of the extracorporeal fluid circuit, while defining withina second panel a second flow path that forms another part of theextracorporeal fluid circuit. The method orients the first and secondpanels in a fluid processing cartridge for mounting as an integratedunit on a fluid processing machine and for removal as an integrated unitfrom the fluid processing machine.

In one embodiment, the method orients the first and second panels in anoverlaying relationship.

Other features and advantages of the inventions are set forth in thefollowing specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a system that enables frequenthemofiltration by supplying to a treatment location a durablehemofiltration machine, a disposable fluid processing cartridge thatfits on the machine, ancillary processing materials that the machine andcartridge use, and telemetry that supports the hemofiltration therapy;

FIG. 2 is a front perspective view of a hemofiltration machine that thesystem shown in FIG. 1 supplies to a treatment location;

FIGS. 3 to 5 are side elevation views showing the loading into themachine shown in FIG. 2 of a fluid processing cartridge, which thesystem shown in FIG. 1 also supplies to the treatment location;

FIG. 6A is a perspective view,of the inside of the door of thehemofiltration machine shown in FIG. 2;

FIG. 6B is a side section view of a spring loaded pump race carried onthe door shown in FIG. 6A, taken generally along line 6B-6B in FIG. 6A;

FIG. 7 is an exploded perspective view of one embodiment of the fluidprocessing cartridge that is supplied to the treatment location,comprising a tray in which a fluid processing circuit is contained;

FIG. 8 is an assembled perspective view of the fluid processingcartridge shown in FIG. 7;

FIG. 9 is a side section view of the fluid processing cartridge shown inFIGS. 7 and 8, showing the cartridge as it is supplied in a closed,sterile condition to the treatment location;

FIG. 10 is a perspective view of the cartridge shown in FIGS. 7 to 9, inpreparation of being mounted on the hemofiltration machine shown in FIG.2;

FIG. 11 is an embodiment of a fluid circuit that the cartridge shown inFIG. 10 can incorporate, being shown in association with the pumps,valves, and sensors of the hemofiltration machine shown in FIG. 2;

FIGS. 12A and 12B are largely schematic side section views of oneembodiment of fluid balancing compartments that can form a part of thecircuit shown in FIG. 11, showing their function of volumetricallybalancing replacement fluid with waste fluid;

FIGS. 13A, 13B, and 13C are perspective views of a bag configured with apattern of seals and folded over to define a overlaying flexible fluidcircuit that can be placed in a fluid processing cartridge of a typeshown in FIG. 11;

FIG. 14 is a plane view of the pattern of seals that the bag shown inFIGS. 13A, 13B, and 13C carries, before the bag is folded over onitself;

FIG. 15 is a plane view of the overlaying fluid circuit that the bagshown in FIG. 14 forms after having been folded over on itself;

FIG. 16 is a largely schematic side section view of the overlaying fluidbalancing compartments that are part of the circuit shown in FIG. 15,showing their function of volumetrically balancing replacement fluidwith waste fluid;

FIG. 17 is a front perspective view of an embodiment of a chassis panelthat the hemofiltration machine shown in FIG. 2 can incorporate;

FIG. 18 is a back perspective view of the chassis panel shown in FIG.17, showing the mechanical linkage of motors, pumps, and valve elementscarried by the chassis panel;

FIG. 19 is a diagrammatic view of a telemetry network that can form apart of the system shown in FIG. 1;

FIG. 20 is a diagrammatic view of overlays for imparting control logicto the machine shown in FIG. 2;

FIG. 21 is an embodiment of a set for attaching multiple replacementfluid bags to the cartridge shown in FIG. 10, the set including anin-line sterilizing filter;

FIG. 22 is a plane view of a graphical user interface that thehemofiltration machine shown in FIG. 2 can incorporate; and

FIG. 23 is a perspective view of a generic user interface which can becustomized by use of a family of interface templates, which thehemofiltration machine shown in FIG. 2 can incorporate.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The various aspects of the invention will be described in connectionwith providing hemofiltration. That is because the features andadvantages that arise due to the invention are well suited to theperformance of hemofiltration. Still, it should be appreciated that thevarious aspects of the invention can be applied to achieve other bloodprocessing objectives as well, such as hemodialysis and hemopheresis.

I. System for Providing Frequent Hemofiltration

FIG. 1 shows a system 10 that makes it possible for a person whose renalfunction is impaired or lacking, to receive convenient andtherapeutically effective hemofiltration on a frequent basis, e.g., atleast four times weekly and, preferably, six times weekly. The frequenthemofiltration therapy that the system 10 provides has as one of itsobjectives the maintenance of uremic toxin levels in the person's bloodwithin a comfortable range, e.g., at no more than 80% of the maximumlevel. Through frequent hemofiltration, the system 10 can provide eitheracute or chronic treatment of renal impairment or failure.

The system 10 delivers the durable and disposable equipment andmaterials necessary to perform frequent hemofiltration on the person ata designated treatment location 12.

The location 12 can vary. It can, for example, be a setting wheresupport and assistance by one or more medically trained care givers areimmediately available to the person, such as at a hospital, anoutpatient clinic, or another treatment center. Alternatively, thelocation 12 can comprise a setting where support or assistance areprovided by a trained partner, such as in the person's residence.

By careful design of durable and disposable equipment, the system 10 canmake it possible for the person to perform frequency hemofiltration in anon-clinical setting, without direct assistance from technically ormedically trained persons.

To make frequent hemofiltration more convenient, the person preferablyhas been fitted with one or more vascular access devices 14. Each device14, for example, may be generally constructed in the manner disclosed inpending U.S. patent application Ser. No. 08/724,948, filed Nov. 20,1996, and entitled “Subcutaneously Implanted Cannula and Method forArterial Access.” The devices 14 preferably support high blood flowrates at or above 300 ml/min and preferably at least 600 ml/min. Thedevices 14 also enable quick and frequent cannulation. The devices 14thereby reduce the time required to set up, perform, and complete afrequent hemofiltration session. The high blood flow rates that thedevices 14 support also increase the removal rate of uremic toxinsduring hemofiltration, as will be described in greater detail later.

To enable frequent hemofiltration, the system 10 supplies to thetreatment location 12 a durable hemofiltration machine 16. The system 10also supplies fluid processing cartridges 18 to the treatment location12, for installation on the machine 16 at the time of treatment. Thesystem 10 further supplies ancillary materials 20, such as replacementfluids, to the treatment location 12 for use in association with thecartridge 18 and machine 16. The system 10 also preferably supplies atelemetry network 22, to enable centralized, off-site monitoring andsupervision of the frequent hemofiltration treatment regime.

The operation of the system 10 to provide these various functions willnow be described in greater detail.

A. Supplying a Hemofiltration Machine

The system 10 includes a source 24 that supplies a hemofiltrationmachine 16 (which can also be called a “cycler”) to the treatmentlocation 12. The machine 16 is intended to be a durable item capable oflong term, maintenance free use.

FIG. 2 shows a representative embodiment of a machine 16 capable ofperforming frequent hemofiltration. The machine 16 is preferablylightweight and portable, presenting a compact footprint, suited foroperation on a table top or other relatively small surface normallyfound, e.g., in a hospital room or in a home. The compact size of themachine 16 also makes it well suited for shipment to a remote servicedepot for maintenance and repair.

In the illustrated embodiment, the machine 16 includes a chassis panel26 and a panel door 28 that moves on a pair of rails 31 in a path towardand away from the chassis panel 26 (as shown by arrows in FIG. 2). Aslot 27 is formed between the chassis panel 26 and the door 28. As FIGS.3 to 4 show, when the door 28 is positioned away from the panel 26, theoperator can, in a simple vertical motion, move a fluid processingcartridge 18 into the slot 27 and, in a simple horizontal motion, fitthe cartridge 18 onto a raised portion of the chassis panel 26. Whenproperly oriented, the fluid processing cartridge 18 rest on the rails31 to help position the cartridge 18. As FIG. 5 shows, movement of thedoor 28 toward the panel 26 engages and further supports the cartridge18 for use on the panel 26 for use. This position of the door 28 will becalled the closed position.

The machine 16 preferably includes a latching mechanism 30 and a sensor32 (see FIG. 2) to secure the door 28 and cartridge against movementbefore enabling circulation of fluid through the cartridge 18.

As will be described in greater detail later, the processing cartridge18 provides the blood and fluid interface for the machine 16.

The machine 16 pumps blood from the person, through the fluid processingcartridge 18 to a hemofilter 34 (mounted in brackets to the side of thechassis panel 26, as shown in phantom lines in FIGS. 2 to 5), back tothe cartridge 18, and then back to the person.

Alternatively, the hemofilter 34 can form an integrated part of thecartridge 18. The hemofilter 34 is connected via the cartridge 18 to theperson's blood supply through the vascular access devices 14.

The machine 16 includes a blood handling unit 36 mounted on the chassispanel 26. The blood handling unit 36 includes a peristaltic blood pump92 and various clamping and sensing devices(described later). The bloodhandling unit 36 circulates the person's blood in a controlled fashionthrough the hemofilter 34 and back to the person. The hemofilter 34removes waste fluid containing urea and other toxins.

The machine 16 also includes a fluid management unit 38 mounted on thechassis panel 26. The fluid management unit 38 includes a peristalticwaste and replacement fluid pump 152 and various clamping and sensingdevices(described later). The fluid management unit 38 replaces thewaste fluid with a sterile replacement fluid, for return with thetreated blood to the person's blood supply. The replacement fluid alsoacts to maintain the person's electrolytic balance and acid/basebalance.

The fluid management unit 38 includes a fluid balancing element 40mounted on the chassis panel 26. The fluid balancing element 40 metersthe return replacement fluid in proportion to the amount of waste fluidremoved.

In the illustrated embodiment, the fluid balancing element 40 includesone or more balancing chambers 206, 208 and associated clampingdevices(the details of which will be described later). The chambers 206,208 comprise preformed depressions formed in the raised portion of thechassis panel 26. As FIG. 6A shows, preformed depressions on the door 28form mating chambers 206′, 208′, which register with the chassis panelchambers 206, 208. When the door 28 is closed, the registered chambers206/206′ and 208/208′ define between them spaces of known volume, e.g.,20 ml. The known volume can, of course, be greater or less than 20 ml,and the chambers 206/206′ and 208/208′ can each have a different knownvolume.

As will be described in greater detail later, flexible containers 212and 214, which form a part of a preformed fluid circuit carried withinthe fluid processing cartridge 18, fit into the registered chambers206/206′ and 208/208′. The chambers 206/206′ and 208/208′ and associatedclamping devices interact with the containers 212 and 214, to providethe capability of balancing waste and replacement fluid volumetrically,in an accurate, straightforward manner, without use of weigh scales andweight sensing.

The machine 16 also includes an ultrafiltration unit 42 on the chassispanel 26. The ultrafiltration unit 42 includes a peristalticultrafiltration pump 144 to remove additional waste from the personwithout addition of replacement fluid. The machine 16 provides, at theend of each frequent hemofiltration session, a net ultrafiltration fluidloss, which coincides with an amount prescribed by the attendingphysician.

The machine 16 completes a frequent hemofiltration session when aprescribed replacement fluid volume has been exchanged and the netultrafiltration fluid loss target has been met. The machine 16 canaccommodate continuous or extended treatment sessions on an automatedbasis. The machine 16 can also accommodate operation based uponindividually set ultrafiltration rates, blood flow rates, or returnfluid flow rates, with completion determined by the volume ofreplacement fluid exchanged or by a treatment timer.

As will be described in greater detail later, the various pumping,clamping, and sensing devices on the machine 16 provide blood flow,fluid management, and safety functions by sensing pump pressures,detecting air, detecting blood leak through the hemofilter 34, andsensing waste pressure. The sensors also provide addition fluidmanagement and safety functions, such as sensing replacement fluidtemperature and replacement fluid pump pressure. The machine 16 alsoprovides other processing functions, such as priming, supplying areplacement fluid bolus, and carrying out a rinseback of the person'sblood.

The machine 16 also preferable includes an operator interface 44, which,in the illustrated embodiment (see FIG. 2) is carried on the exterior ofthe door 28. As will be described later, the interface 44 providessimple switch and/or knob operation of the machine 16, preferably by useof one hand. The interface 44 displays information necessary to operatethe machine 16, presenting an uncluttered display and tactile touchbuttons to intuitively lead a person without technical or medicalbackground through set up and operation of the machine 16 with a minimumof training.

Further details of the machine 16, the pumps and sensing devices, andtheir interaction with the fluid processing cartridge 18 will bedescribed later.

The source 24 supplying the machine 16 can comprise a company orbusiness that manufactures the machine 16 or otherwise distributes themachine 16 to the treatment location 12 on a sale, lease, or rentalbasis.

B. Supplying a Fluid Processing Cartridge

The system 10 further includes a source 46 for supplying a fluidprocessing cartridge 18 to the treatment location 12 for use inassociation with the machine 16. The cartridge 18 is intended to bedisposable item, capable of single or extended use, which the loads onthe machine 16 before beginning a hemofiltration session (as FIGS. 3 to5 show). The cartridge 18 can be removed from the machine 16 anddiscarded upon the completing the hemofiltration session, or its use canbe extended to one or more subsequent sessions, as will be describedlater.

The cartridge 18 couples to the person's vascular access devices 14 andinteracts with the machine 16 to draw, process, and return blood in acontinuous, extracoporeal path, to carry out fluid balancing throughwaste removal, replacement fluid exchange, and ultrafiltration.

Preferably, the tasks of loading and unloading the cartridge 18 aresimple and straightforward, following a simple, straight loading andunloading path into the slot 27 and against the chassis panel 26, asFIGS. 3 to 5 show. In this way, the person receiving hemofiltration canby himself/herself set up the cartridge 18 and machine 16, withoutnecessarily requiring assistance from a technically or medically trainedperson.

The cartridge 18 preferably provides the entire blood and fluidinterface for the machine 16, including all pumping, valving, pressuresensing, air detection, blood leak detection, and tubing management. Thecartridge 18 preferable is supplied to the treatment location 12 withall tubing, access needles and waste and replacement fluid connectionspreconnected. A waste bag also can be preattached, if desired, or thewaste line can be placed in a drain.

Loading the cartridge 18 on the chassis panel 26 and closing the door 28also automatically locates all sensors of the machine's safety functionin association with the blood fluid interface. The operator is notrequired to load anything else to carry out the machine's safetyfunction. Once the machine 18 undergoes start up testing to confirmcartridge placement and integrity and to confirm the functionality ofthe sensors, subsequent automated operation the machine 18 in a safemode is assured.

The cartridge 18 can be constructed in various ways. In the illustratedembodiment (see FIGS. 7 to 9), the cartridge 18 includes a preformedtray 48 and insert 53 manufactured, e.g., by thermoforming polystyreneor another comparable material. The tray 48 and insert 53 areperipherally joined together, e.g., by ultrasonic welding.

The tray includes a base 50, side walls 52, and an open top edge 54. Thegeometry of the tray 48 is appropriately keyed to fit in only oneorientation on the rails 31 in the slot 27 between the chassis panel 26and door 28 of the machine 16. When so fitted, the insert 53 rests onthe raised portion of the chassis panel 26. Closing the door 28 securesthe tray 48 to the panel 26.

A preformed circuit 56 is carried between the base 50 of the tray 48 andthe insert 53. The circuit 56 is arranged to carry blood, waste, andreplacement fluid during hemofiltration.

As will be described in greater detail later, the circuit 56 includes anarray of fluid flow paths formed with in-line flexible containers 212and 214 (for fluid balancing), peristaltic pump headers, sensorstations, tubing, and valve stations. The layout of flow paths,containers, pump headers, sensing stations, and valve stations on thecircuit 56 form a mirror image of the layout of the structural andmechanical components on the chassis panel 26 and door 28 of the machine16.

The insert 53 includes cut outs 58 to expose the containers, peristalticpump headers, sensing stations, and valve stations for engagement withequipment on the chassis panel 26. When the tray 48 is fitted to thechassis panel 26, and the door 28 is closed, the in-line containers212/214 formed in the circuit 56 fit within the registered chambers206/206′ and 208/208′ on the chassis panel 26 and door 28. Likewise, thepump headers and the sensor and valve stations on the circuit 56 overlayand engage corresponding peristaltic pumps, sensors, and valve on thechassis panel 26.

In the illustrated embodiment (see FIG. 7), the base 50 of the tray 48underlaying the pump stations is relieved, to form pump races 360. Theinside surface of the door 28 carries concave pump races 362 supportedby springs 364 (see FIGS. 6A and 6B). When the door 28 is closed, thespring loaded pump races 362 on the door 28 nest with the relieved pumpraces 360 on the tray 48, to provide rigidity and support.Alternatively, the pump races 360 can form cutouts in the base 50 (likecut outs 58 in the insert, as earlier described), through which the pumpraces 362 on the door 28 extend.

The base 50 of the tray 48 underlying the containers 212/214 is alsorelieved, to form chamber supports 368. When the the door 28 is closed,the tray supports 368 fit within the door chambers 206′ and 208′. Thedoor 28 therefore engages the tray 48, to add overall rigidity andsupport to the tray base 50.

When the door 28 is closed, the containers 212/214 are enclosed withinthe registered chambers 206/206′ and 208/208′ and tray chamber supports368, which define for the containers 212/214 to a known maximum volume.The peristaltic pumps, sensors, and valve stations on the machine 16interact with the flexible components of the circuit 56.

The cartridge 18 makes possible direct, centralized connection of ablood-fluid interface to the blood pump, the waste and replacement pump,the ultrafiltration pump, the fluid balancing chambers, the sensordevices, and the clamping devices of the machine 16, with no airinterfaces. The compact arrangement of the cartridge 18 also reducesfluid pressure drops, thereby accommodating high flow rates, e.g., anarterial blood line pressure drop of less than 250 mmHg at a flow rateof 600 ml/min and a hematocrit of 25.

As FIGS. 9 and 10 show, lengths of flexible tubing FT are coupled to thecircuit 56 in the base 50 of the tray 48 and rest in coils on top of theinsert 53 within the tray 48 during shipment and before use (see FIG.9). As FIG. 9 also shows, a removable lid 60, made, e.g., from ethyleneoxide permeable TYVEKJ material or polyethylene plastic sheet stock,covers and seals the interior of the tray 48 prior to use. The cartridge18 can therefore be sterilized by exposure to ethylene oxide prior touse. Other methods of sterilization, e.g., gamma radiation or steamsterilization, can be used. Alternatively, the ultrasonically weldedassembly of the tray 58, insert 53, and the circuit 56 (with attachedtubing FT) can be packaged as a unit into a sealed plastic bag forsterilization, obviating the need for the lid 60.

At the instant of use, the lid 60 is peeled away, or, in the alternativearrangement, the sealed plastic bag is opened. The attached flexibletubing FT is extended beyond the bounds of the tray 48 to makeconnection with external processing items (see FIG. 10). The tubing FTcarries appropriate couplers for this purpose. The tray 48 is movedalong a vertical path for loading into the slot 27 and then a horizontalpath for loading on the raised portion of the chassis panel 26, afterwhich a simple motion of the door latching mechanism 30 aligns theentire fluid circuit 56 with the pumps, sensors, and clamps on thechassis panel 26. There is no area of blood or fluid contact that thisoutside the disposable circuit 56.

The source 46 supplying the cartridge 18 can comprise a company orbusiness that manufactures the cartridge 18 or that otherwisedistributes the cartridge 18 to the treatment location 12 on a sale,lease, or rental basis.

1. Fluid Circuit for Frequent Hemofiltration

FIG. 11 shows a representative fluid circuit 56 that is well suited forcarrying out frequent hemofiltration, and which can be incorporated intothe cartridge 18 for interface with pumps, valves, and sensors arrangedas a mirror image on the chassis panel 26.

The fluid circuit 56 couples the hemofilter 34 to several main fluidflow paths. The main fluid flow paths comprise an arterial blood supplypath 62, a venous blood return path 64, a blood waste path 66, areplacement fluid path 68, and an ultrafiltration/fluid balancing path70.

(i) Blood Supply and Return Paths

The arterial blood supply path 62 and venous blood return path 64includes lengths of flexible tubing 72 and 74 that extend outside thetray 48 (see FIG. 10). As FIG. 10 shows, The paths 72 and 74 carrycannulas 76 at their distal ends (or connectors that enable connectionto cannulas 76), to enable connection, respectively, to the person'sarterial and venous access devices 14.

The arterial blood supply path 62 also includes a length of flexibletubing 78 (see FIG. 10) that extends outside the tray 48. The tubing 78includes a distal connector 80 to couple to the blood inlet 82 of thehemofilter 34.

Likewise, the venous blood return path 64 includes a length of flexibletubing 84 that extends outside the tray 48. The tubing 84 includes adistal connector 86 to couple to the blood outlet 88 of the hemofilter34.

Alternatively, the hemofilter 34 can be an integral part of the tray 48.In this arrangement, the arterial and venous blood paths 78 and 84 aresupplied pre-connected to the hemofilter 34.

The exterior tubing components of the arterial or venous blood paths caninclude injection sites 90. The sites can be used, e.g., to removetrapped air or to inject anticoagulant, medication, or buffers into theblood flows. The exterior tubing components of the arterial or venousblood paths can also include conventional pinch clamps, to facilitatepatient connection and disconnection.

The remaining portions of arterial and venous blood paths 62 and 64 arecontained in the circuit 56 held within the tray 48. The blood pump 92of the machine 16 engages a pump header region 94 in the arterial bloodsupply path 62 within the tray 48 upstream of the hemofilter 34, toconvey blood into and through the hemofilter 34. An arterial blood clamp96 and a patient connection-disconnection (air bubble detector) sensor98 on the machine 16 engage a clamp region 100 and a sensor region 102in the arterial blood supply path 62 within the tray 48 upstream of theblood pump 92. Alternatively, an air bubble sensor (not shown) can belocated downstream of the blood pump 92 and upstream of the hemofilter34.

The placement of the air sensor 98 upstream of the hemofilter 34 allowsair bubbles to be detected prior to entering the hemofilter 34. In thehemofilter 34, air bubbles break up into tiny micro-bubbles, which arenot as easily detected. Placement of the air sensor 98 upstream of thehemofilter 34 also serves the additional purpose of detecting air whenthe blood pump 92 is operated in reverse, to rinse back blood to thepatient, as will be described later.

An air detector 108 on the machine 16 engages a sensing region 110 inthe venous blood return path 64 within the tray 48 downstream of thehemofilter 34. A venous clamp 112 on the machine 16 engages a clampregion 114 in the venous blood return path 64 within the tray 48downstream of the air detector 108.

(ii) Blood Waste Path

The membrane (not shown) located in the hemofilter 34 separates wasteincluding liquid and uremic toxins from the blood. A waste outlet 116conveys waste from the hemofilter 34.

The blood waste path 66 includes a length of flexible tubing 118 (seeFIG. 10) that extends beyond the tray 48. The tubing 118 carries adistal connector 120 to couple to the waste outlet 116 of the hemofilter34. Alternatively, when the hemofilter 34 is integrated in the tray 48,the waste path 66 can be supplied pre-connected to the hemofilter 34.

The waste path 66 also includes a length of flexible tubing 122 thatextends beyond the tray 48. The tubing 122 carries a connector 124 tocouple to a waste bag 126 or an external drain. Alternatively, the wastebag 126 can be preconnected to the tubing 122.

The remainder of the waste path 66 is contained within the circuit 56inside the tray 48. A blood leak detector 128 on the machine 16 engagesa sensor region 130 in the waste path 66 downstream of the hemofilter34. A waste pressure sensor 132 on the machine 16 engages another sensorregion 134 in the waste path 66 downstream of the blood leak detector128.

Within the tray 48, the waste path 66 branches into an ultrafiltrationpath 136 and a balancing path 138. The ultrafiltration branch path 136bypasses in-line containers 212 and 214 of the circuit 56. Theultrafiltration pump 144 on the machine 16 engages a pump header region146 in the ultrafiltration branch path 136 within the tray 48. The wastebalancing branch path 138 communicates with the in-line containers 212and 214. The waste and replacement fluid pump 152 on the machine 16engages a pump header region 154 in the waste balancing branch path 138within the tray 48 upstream of the in-line containers 212 and 214. Apressure sensor 156 on the machine 16 engages a sensor region 160 in thewaste balancing branch path 138 within the tray 48 between the waste andreplacement fluid pump 152 and the in-line containers 212 and 214. Thepressure sensor 156 senses the fluid pressure required to conveyreplacement fluid into the venous return line. This resistance to theflow of replacement fluid is the venous blood pressure. The pressuresensor 156 in the waste fluid path 138 thereby serves to sense thevenous blood pressure.

A flush clamp 162 engages a clamp region 164 in the waste path 66 withinthe tray 48 downstream of the in-line containers 212 and 214. A wasteclamp 166 engages a clamp region 168 in the waste path 66 downstream ofthe flush clamp 162. The circuit 56 in the tray 48 also can include anair break 170, which communicates with the waste path 66 downstream ofthe waste clamp 166. The air break 170 prevents back flow ofcontaminants into the circuit 56 from the waste bag 126 or drain.

(iii) Replacement Fluid Path

The replacement fluid path 68 includes a length of flexible tubing 172that extends outside the tray 48. The tubing 172 includes a distalconnector 174 or connectors that enable connection to multiplecontainers of replacement fluid 176. As will be described later, thetubing 172 can also include an in-line 0.2 m sterilizing filter 178 toavoid contamination of-the circuit 56.

The containers 176 together typically hold from 8 to 20 combined litersof replacement fluid, depending upon the fluid removal objectives of theparticular frequent hemofiltration procedure. The replacement fluid isalso used to prime the fluid circuit 56 at the outset of a treatmentsession and to rinse back blood to the patient at the end of a treatmentsession.

The remainder of the replacement fluid path 68 is contained in thecircuit 56 within the tray 48. Sensing region 186 in the replacementfluid path 68 inside the tray 48 engages a replacement fluid flow ratedetector 182 on the machine 16. A clamping region 190 in the replacementfluid path 68 inside the tray 48 engages a replacement fluid clamp 188on the machine 16.

Within the tray 48, the replacement-fluid path 68 includes a priming orbolus branch path 192 that communicates with the arterial blood supplypath 62. A clamping region 196 in the priming branch path 192 engages apriming clamp 194 on the machine 16.

Within the tray 48, the replacement fluid path 68 also includes abalancing branch path 198 that communicates with the venous blood returnpath 64, via the in-line containers 212 and 214. A pump header region200 in the balancing replacement branch path 198 engages the waste andfluid replacement pump 152 on the machine 16 upstream of the in-linecontainers 212 and 214.

In the illustrated embodiment, the waste and fluid replacement pump 152comprises a dual header pump, simultaneously engaging the two pumpheader regions 154 and 200 on the waste path 66 and the replacementfluid path 68. A sensor region 204 in the balancing replacement branchpath 198 engages a pressure sensor 202 on the machine 16 between thewaste and replacement fluid pump 152 and the in-line containers 212 and214. The pressure sensor 202 senses the pressure required to conveywaste fluid into the waste return line. This resistance to the flow ofwaste fluid is the waste line pressure. The pressure sensor 202 in thereplacement fluid path 198 thereby serves to sense the waste linepressure. Similarly, as already described, the pressure sensor 156 inthe waste fluid path 138 serves to sense the venous blood pressure.

(iv) Ultrafiltration/Fluid Balancing Path

The ultrafiltration waste branch path 136 within the tray 48, whichbypasses the in-line containers 212 and 214 of the circuit 56,accommodates transfer of a prescribed volume of waste to the waste bag126, without an offsetting volume of replacement fluid. The circuit 56thereby is capable of performing an ultrafiltration function.

The balancing waste branch path 138 and the balancing replacement branchpath 198 pass through the in-line containers 212 and 214 in the circuit56 contained within the tray 48. The in-line containers 212 and 214transfer a volume of replacement fluid to the venous blood return path64 in proportion to the volume of waste fluid removed, except for thevolume making up the ultrafiltration volume loss. The circuit 56 isthereby capable of performing a fluid balancing function in addition tothe ultrafiltration function.

In the illustrated embodiment, the machine 16 and circuit 56 carry outthe fluid balancing function volumetrically, without weight sensing.More particularly, the registered chambers 206/206′ and 208/208′ on thechassis panel 26 and door 28, of the machine 16 receive the in-linecontainers 212 and 214 when the tray 48 is mounted on the chassis panel26. The registered chambers 206/206′ and 208/208′ mutually imposevolumetric constraints on the in-line containers 212 and 214, to definea maximum interior volume for each of the on-line containers 212 and214. In the illustrated embodiment, when facing the chassis panel 26,the container 212 is situated on the left side (in registered chambers206/206′) and the container 214 is situated on the right side (inregistered chambers 208/208′). FIGS. 12A and 12B show one embodiment ofthe right and left orientation of the containers 212 and 214, with thecontainers 212 and 214 also shown in side section.

In the embodiment shown in FIGS. 12A and 12B, each in-line container 212and 214 is itself divided along their midline from front to back by aninterior flexible wall 210, to form four compartments. As FIG. 12A and12B show, two of the compartments face the door 28, and are thusdesignated as front compartments 212F and 214F. The other twocompartments face the chassis panel 26, and will thus be designed asrear compartments 212R and 214R.

Each in-line container 212 and 214 has a waste side compartmentcommunicating with waste path 66 and a replacement side compartmentcommunicating with the replacement fluid path 68. In the illustratedembodiment, the circuit 56 establishes communication between thebalancing waste branch path 138 and the rear compartments 212R and 214R(which will also be called the waste side compartments). The circuit 56also establishes communication between the balancing replacement branch.path 198 and the front compartments 212R and 214R (which will also becalled the replacement side compartments). In the embodiment illustratedin FIGS. 12A and 12B, fluid enters the compartments from the bottom andexits the compartments from the top. Other flow paths into and from thecompartments can be established, as will be described later.

The machine 16 includes an inlet valve assembly 216 and an outlet valveassembly 218 on the chassis panel 26, located in association with thechambers 206 and 208. The circuit 56 in the tray 48 likewise includes,for each in-line container 212 and 214, an inlet clamp region 220 and anoutlet clamp region 222, which govern flow into and out of the wasteside compartments 212R and 214R. The circuit 56 in the tray 48 alsoincludes, for each in-line container 212 and 214, an inlet clamp region224 and an outlet clamp region 226, which govern flow into and out ofthe replacement side compartments 212F and 214F.

When the tray 48 is mounted on the chassis panel 26, the inlet andoutlet valve assemblies 216 and 218 on the machine 16 engage thecorresponding waste and replacement fluid inlet and outlet clamp regions220, 222, 224, 226 in the circuit 56. The machine 16 toggles theoperation of inlet and outlet valve assemblies 216 and 218 tosynchronize the flow of fluids into and out of the waste side andreplacement side compartments of each in-line container 212 and 214.

More particularly, for a given in-line container 212 and 214, in a firstvalve cycle (see FIG. 12A), the waste side inlet valve 220 is openedwhile the waste side outlet valve 222 is closed. Waste fluid is conveyedby operation of the waste and replacement pump 152 from the waste path66 into the waste side compartment of the given in-line container 212and 214. Simultaneously, for the same in-line compartment 212 and 214,the replacement side inlet valve 224 is closed and the replacement sideoutlet valve 226 is opened, so that the incoming flow of waste in thewaste side compartment displaces the interior wall 210 to express a likevolume of replacement fluid from the replacement side compartment intothe venous blood return path 64.

In a subsequent cycle for the same in-line container 212 and 214, anopposite valve action occurs (see FIG. 12B). The replacement side inletvalve 224 is opened and the replacement side outlet valve 226 is closed,and replacement fluid is conveyed into the replacement side compartmentfrom the replacement fluid path 68. The incoming replacement fluiddisplaces the interior wall 210 to express a like volume of waste fluidfrom the waste side compartment to the waste bag 126 (the waste sideinlet valve 220 now being closed and the waste side outlet valve 222 nowbeing opened).

As FIGS. 12A and 12B show, the valve assemblies work in tandem upon thetwo in-line containers 212 and 214, with one container 140 receivingwaste and dispensing replacement fluid, while the other container 142receives replacement fluid and dispenses waste, and vice versa. In thisway, the circuit 56 provides a continuous, volumetrically balanced flowof waste fluid to the waste bag 126 and replacement fluid to the venousblood return path 64.

2. A Circuit Contained in a Double Panel Bag

The function of the fluid circuit 56 shown in FIGS. 11, 12A, and 12B canbe realized in various ways. FIGS. 13A to 13C show a fluid circuit bag228 made from two overlaying sheets 230A and 230B of flexible medicalgrade plastic, e.g., poly vinyl chloride (see FIG. 13A). When laid flat(see FIG. 13B), the bag 228 defines first and second panels 232 and 234divided along a midline 236. By folding the bag 228 about its midline236 (see FIG. 13C), the first and second panels 232 and 234 are broughtinto registration in a reverse facing relationship, with one panel 232comprising the front of the bag 228 and the other panel 234 comprisingthe back of the bag 228.

The first and second panel 232 and 234 each includes an individualpattern of seals S formed, e.g., by radio frequency welding. The seals Sform fluid flow paths, including the in-line containers 212 and 214,peristaltic pump header regions, the sensor regions, and clamp regionspreviously described. The flow paths formed by the pattern of seals Scan comprise all or part of the circuit 56. Pump header tubing lengths155, 145, and 201 are sealed in placed within the seal pattern S to formthe pump regions 154, 146, and 201, respectively.

In the illustrated embodiment, as FIG. 14 shows, the seals S on thefirst panel 232 are configured to form the flow paths of the circuit 56through which replacement fluid is conveyed from the replacement fluidpath 68 to the venous blood return path 64, including the left and rightfront-facing replacement fluid compartments 212F and 214F. The seals Son the second panel 234 are configured to form the flow paths of thecircuit 56 through which waste fluid is conveyed from the waste path 66to the waste bag 126 or drain, including the left and right rear-facingwaste fluid compartments 212R and 214R. Seals S form four individualcontainers, two containers 212F and 214F on the panel 232, and twocontainers 212R and 214R on the panel 234.

Once the seal patterns S are formed, the bag 228 is folded over aboutits midline 236 (see FIG. 15). The bag 228 places in close associationor registry the waste and replacement fluid paths 66 and 68 of thecircuit 56. The replacement fluid paths 68 of the circuit 56 occupy thefront panel 232 of the bag 228, and the waste paths 66 of the circuit 56occupy the back panel 234 of the bag 228 (or vice versa, depending uponthe desired orientation of the bag 228).

In use, the folded over bag 228 is contained in the base 50 of the tray48, with portions exposed through cutouts 58 in the insert 51 forengagement with the machine peristaltic pumps, sensing elements, andclamping elements, in the manner shown in FIG. 10. The remainingportions of the circuit 56 not contained within the bag 228 are formedof tubing and fit into preformed areas in the base 50 of the tray 48 (orformed within another bag) and coupled in fluid communication with theflow paths of the bag 228, to complete the circuit 56 shown in FIG. 10.

The flow paths formed on the first panel 232 include the balancereplacement fluid paths 198, which lead to and from the replacement sidecompartments 212F and 214F. In the tray 48, the replacement sidecompartments 212F and 214F rest in recesses in the tray base 50. Cutouts58 in the insert 51 expose the pump header regions 200 and 154, toengage the peristaltic waste and replacement pump 152 on the machine 16;the inlet clamp regions 224, to engage the inlet valve assembly 216 onthe machine 16 to control inflow of replacement fluid into thereplacement side compartments 212F and 214F; and the outlet clampregions 226, to engage the outlet valve assembly 218 on the machine 16to control outflow of replacement fluid from the replacement sidecompartments 212F and 214F. The cutouts 58 also expose the sensor region204, to engage the pressure sensor 202 downstream of the waste andreplacement pump 152, and a pressure relief path 240 with exposedpressure relief bypass valve 242, the purpose of which will be describedlater. A small opening 203 formed in the pump header tubing 201 openscommunication with the relief path 240.

The flow paths formed on the second panel 234 (shown in phantom lines inFIG. 15) include the waste path 138 that lead to and from the waste sidecompartments 212R and 214R (for fluid balancing) and the waste path 136that bypasses the waste side compartments 212R and 214R (forultrafiltration). As FIG. 15 shows, when the bag 228 is folded over inthe tray 48, the waste compartments 212R and 214R on the waste panel 234and the replacement compartments 212F and 214F on the replacement panel232 overlay, so both are exposed through the cutout 58 in the insert forregistry as a unit with the chambers 206 and 208 on the chassis panel26.

The flow paths on the waste panel 234 also include the exposed wasteinlet clamp regions 220, to engage the valve assembly 218 to controlinflow of waste fluid into the waste compartments 212R and 214R, and theexposed waste outlet clamp regions 222, to engage the valve assembly 216to control outflow of waste fluid from the waste compartments 212R and214R. When the bag 228 is folded over in the tray 48, the inlet clampregions of the waste compartments 212R and 214R formed on the wastepanel 234 overlay the outlet clamp regions of the replacementcompartments 212F and 214F formed on the replacement panel 232, and viceversa.

The flow paths also includes an exposed pump header region 154, toengage the peristaltic waste and replacement pump 152. When the bag 228is folded over in the tray 48, the exposed pump header regions 200 and154 on the replacement and waste panels 232 and 234 lay side-by-side, toaccommodate common engagement with the dual header waste and replacementpump 152. The flow paths also include the sensor region 160, to engagethe pressure sensor 156 downstream of the waste and replacement fluidpump 152.

The flow paths also include the pump header region 146, to engage theperistaltic ultrafiltration pump 144. When the bag 228 is folded over inthe tray 48, the exposed pump header region 146 for the ultrafiltrationpump 144 is spaced away from the other pump header regions of thecircuit 56.

In FIGS. 12A and 12B, the entry paths serving the waste and replacementcompartments are located at the bottom, while the exit paths serving thewaste and replacement compartments are located at the top. Thisconfiguration facilitates priming of the compartments. Still, the spacedapart configuration requires eight valve assemblies.

In FIG. 16, the entry and exit paths serving the waste and replacementcompartments are all located at the top. Priming is still achieved, asthe paths are top-oriented. Furthermore, due to the folded-overconfiguration of the bag itself, the clamping regions 220, 222, 226 canbe arranged overlay one another. The overlaying arrangement of theclamping regions 220, 222, 224, and 226 serving the waste andreplacement compartments simplifies the number and operation of theinlet and outlet valve assemblies 216 and 218 on the machine 16. Sincethe inlet clamp regions 224 for the replacement compartments 212F and214F overlay the outlet clamp regions 222 for the waste compartments212R and 214R, and vice versa, only four clamping elements 244, 246,248, 250 need be employed to simultaneously open and close theoverlaying eight clamp regions (see FIG. 16). By further stacking (notshown) of the compartments, the clamping elements could be reduced totwo.

As FIG. 16 shows, the first clamping element 244 is movable intosimultaneous clamping engagement with the inlet clamp region 224 of theleft replacement compartment 212F (on the replacement panel 232) and theoutlet clamp region 222 of the left waste compartment 212R (on the wastepanel 234), closing both. Likewise, the fourth clamping element 250 ismovable into simultaneous clamping engagement with the inlet clampregion 224 of the right replacement compartment 214F (on the replacementpanel 232) and the outlet clamp region 222 of the right wastecompartment 214R (on the waste panel 234), closing both.

The second clamping element 246 is movable into simultaneous clampingengagement with the outlet clamp region 226 of the left replacementcompartment 212F (on the replacement panel 232) and the inlet clampregion 220 of the left waste compartment 212R (on the waste panel 232),closing both. Likewise, the third clamping element 248 is movable intosimultaneous clamping engagement with the outlet clamp region 226 of theright replacement compartment 214F (on the replacement panel 232) andthe inlet clamp region 220 of the right waste compartment 214R (on thewaste panel 234), closing both.

The machine 16 toggles operation of the first and third clampingelements 244, 248 in tandem, while toggling operation the second andfourth clamping elements 246, 250 in tandem. When the first and thirdclamping elements 244, 248 are operated to close their respective clampregions, replacement fluid enters the right replacement compartment 214Fto displace waste fluid from the underlying right waste compartment214R, while waste fluid enters the left waste compartment 212R todisplace replacement fluid from the overlaying left replacementcompartment 212F. When the second and fourth clamping elements 246, 250are operated to close their respective clamp regions, replacement fluidenters the left replacement compartment 212F to displace waste fluidfrom the underlying left waste compartment 212R, while waste fluidenters the right waste compartment 214R to displace replacement fluidfrom the overlaying right replacement compartment 214F.

FIGS. 17 and 18 show a mechanically linked pump and valve system 300that can be arranged on the chassis panel 26 and used in associationwith the layered fluid circuit bag 228 shown in FIG. 15.

The system 300 includes three electric motors 302, 304, and 306. Thefirst motor 302 is mechanically linked by a drive belt 308 to the dualheader waste and replacement pump 152, previously described. The secondmotor 304 is mechanically linked by a drive belt 310 to the blood pump92, also previously described. The third motor 306 is mechanicallylinked by a drive belt 312 to the ultrafiltration pump 144, also aspreviously described.

A drive belt 314 also mechanically links the first motor to the first,second, third, and fourth clamping elements 244, 246, 248, and 250, viaa cam actuator mechanism 316. The cam actuator mechanism 316 includes,for each clamping element 244, 246, 248, and 250 a pinch valve 318mechanically coupled to a cam 320. The cams 320 rotate about a driveshaft 322, which is coupled to the drive belt 314.

Rotation of the cams 320 advances or withdraws the pinch valves 318,according to the surface contour machined on the periphery of the cam320. When advanced, the pinch valve 318 closes the overlying clampregions of the fluid circuit bag 228 that lay in its path. Whenwithdrawn, the pinch valve 318 opens the overlying clamp regions.

The cams 320 are arranged along the drive shaft 322 to achieve apredetermined sequence of pinch valve operation. During the sequence,the rotating cams 320 first simultaneously close all the clampingelements 244, 246, 248, and 250 for a predetermined short time period,and then open clamping elements 244 and 248, while closing clampingelements 246 and 250 for a predetermined time period. The rotating cams320 then return all the clamping elements 244, 246, 248, and 250 to asimultaneously closed condition for a short predetermined time period,and then open clamping elements 246 and 250, while closing clampingelements 244 and 248 for a predetermined time period.

The sequence is repeated and achieves the balanced cycling ofreplacement fluid and waste fluid through the containers 212 and 214, aspreviously described. A chamber cycle occurs in the time interval thatthe valve elements 244, 246, 248, and 250 change from a simultaneouslyclosed condition and return to the simultaneously closed condition.

The cam actuator mechanism 316 mechanically links the clamping elements244, 246, 248, and 250 ratiometrically with the first motor 302. As themotor 302 increases or decreases the speed of the dual header waste andreplacement pump 152, the operation of the clamping elements 244, 246,248 and 250 increases or decreases a proportional amount.

In a preferred embodiment, the ratio is set so that the flow rate perunit time through the waste pump header region 154 (i.e., through wastepath 66) approximately equals three-fourths of the volume of the wastecompartment 212R/214R, while maintaining the cycle rate at less than 10cycles per minute. For example, if the chamber volume is 20 cc, thecycle occurs after 15 to 17 cc of waste fluid enters the compartment.

In the illustrated embodiment, the waste pump header region 154 is madesmaller in diameter than the replacement fluid header region 200. Thus,during operation of the dual header pump 152, the flow rate through thereplacement fluid header region 200 (through replacement fluid path 68)will always be larger than the flow rate through the waste pump headerregion 154 (through waste path 68). Due to the high flow rate throughthe replacement fluid path 68, a pressure relief path 240 with pressurerelief bypass valve 242 is provided, to prevent overfilling. In theillustrated embodiment, the valve 242 is a mechanically spring biasedpressure regulator, and serves the pressure regulation and bypassfunction of the machine 16.

In this arrangement, the in-line compartment that receives waste fluidwill fill to approximately three-fourths of its volume during eachcycle, displacing an equal amount of replacement fluid from itscompanion compartment. At the same time, the other in-line compartmentthat receives replacement fluid will fill completely. If the compartmentcompletely fills with replacement fluid before the end of the cycle, thepressure relief bypass valve 242 will open to circulate replacementfluid through the relief path 240 to prevent overfilling. During thenext cycle, waste fluid in the compartment will be completely displacedby the complete fill of replacement fluid in its companion compartment.

The provision of a higher flow rate in the replacement fluid path alsofacilitates initial priming (as will be described later). Only severalchamber cycles are required to completely prime the in-line containers212 and 214 with replacement fluid before fluid balancing operationsbegin.

The pump and valve system 300 used in association with the layered fluidcircuit bag 228 achieves accurate fluid balancing during frequenthemofiltration. Due to the smaller volumes of replacement fluid requiredduring each frequent hemofiltration session, slight variations that mayoccur (e.g., plus or minus 5%) between fluid volume removed and fluidvolume replaced do not lead to large volume shifts. As a result ofaccurate balancing of small fluid volumes, a person undergoing frequenthemofiltration does not experience significant day-to-day swings in bodyfluid volume, and more precise control of the person's body fluid andweight can be achieved.

C. Supplying Ancillary Materials

The system 10 further includes a source 252 or sources that supplyancillary materials 20 to the treatment location 12 for use inassociation with the cartridge 18 and machine 16. The ancillarymaterials 20 include the replacement fluid containers 176, as prescribedby the person's physician.

The ancillary materials 20 may also include an anticoagulant prescribedby a physician. However, anticoagulant may not be required for everyperson undergoing frequent hemofiltration, depending upon treatmenttime, treatment frequency, blood hematocrit, and other physiologicconditions of the person.

The ancillary materials 20 can also include the hemofilter 34, although,alternatively, the tray 48 can carry the hemofilter 34, or thehemofilter 34 can -comprise an integrated component of the cartridge 18.

Through operation of the machine 16, cartridge 18, and ancillarymaterials 20 supplied by the system 10, the person's blood is conveyedthrough the hemofilter 34 for removal of waste fluid containing urea andother toxins. Replacement fluid is exchanged for the removed wastefluid, to maintain the person's electrolyte balance and acid/basebalance. The replacement fluid is also balanced against an additionalwaste fluid removal, to yield a net ultrafiltration loss, as prescribedby the person's physician.

The composition of an optimal replacement fluid solution usable duringfrequent hemofiltration consist of a balanced salt solution containingthe major cationic and anionic plasma constituents, includingbicarbonate or another anion from which net bicarbonate can be generatedby metabolism. Specific cationic substances removed by frequenthemofiltration that require replacement typically include sodium,potassium and calcium. Specific anionic substances removed by frequenthemofiltration that require replacement include chloride and eitherbicarbonate or another anion that can be metabolized into bicarbonate,such as acetate, citrate, or, typically, lactate.

The replacement fluid for frequent hemofiltration should excludephosphorus and other anionic substances. These materials typicallyaccumulate in undesirable amounts in persons experiencing renal failureand are either difficult to remove in large amounts duringhemofiltration or are safely removed without need for specificreplacement.

The concentration of sodium in a replacement fluid for frequenthemofiltration should fall slightly below that of the typical bloodfiltrate concentration of 135 to 152 meq/liter. The optimal range forsodium in the replacement fluid for frequent hemofiltration is 128-132meq/liter, and typically 130 meq/liter. This concentration allows for anet sodium removal during frequent hemofiltration sessions, which iseasily tolerated due to the smaller replacement fluid volumes necessaryfor frequent hemofiltration. This concentration also results in aminimal net drop in serum osmolality, so as to decrease extracellularvolume to a extent sufficient to maintain euvolemia while amelioratingthirst in the person undergoing frequent hemofiltration.

The metabolism of calcium is quite complicated and much lessstraightforward than sodium. Thus, the optimal concentration in areplacement fluid for frequent hemofiltration should be much closer tothe normal physiologic range of calcium in plasma, i.e., in a range of2.5 to 3.5 meq/liter, and typically 2.7 meq/liter. This calciumconcentration range is required to prevent tetany, which can result fromexcessive removal of ionized calcium, while removing excessive serumcalcium that may result from the oral calcium supplements and phosphorusbinders frequently used by persons requiring hemofiltration.

Selecting an optimal concentration of potassium in a replacement fluidfor frequent hemofiltration is important. Typically, the potassiumconcentrations selected for replacement fluids used during infrequenthemofiltration (3 times a week or less) or during hemodialysis are quitelow, e.g., in the range of 0 to 3 meq/liter. These low concentrations ofpotassium are required for infrequent hemofiltration therapies, toprevent life threatening accumulations of serum potassium betweentreatment sessions. Interim accumulation of toxic levels of potassiumcan be encountered between infrequent hemofiltration sessions, bothbecause of decreased renal excretion of potassium and the interimdevelopment of acidosis between sessions. This, in turn, can result intotal body potassium depletion in many persons undergoing infrequenttherapy. Potassium depletion results in vasoconstriction and subsequentalterations in regional blood flow. Potassium depletion also interfereswith the efficiency of solute removal, as measured by a decrease in Kt/Vfor urea, which is a dimensionless parameter commonly employed tomeasure the adequacy of dialysis. Potassium depletion is also implicatedin the pathogenesis of hypertension in patients undergoing hemodialysisor infrequent hemofiltration.

In contrast, the optimal range for potassium in a replacement fluid usedfor frequent hemofiltration can fall in a higher range than thatrequired of less frequent treatment schedules, laying in the range of2.7 to 4.5 meq/liter, and typically 4.0 meq/liter. This higherconcentration of potassium, when infused frequently in smaller fluidreplacement volumes, prevents potassium depletion, while alsomaintaining more stable potassium levels to prevent toxic accumulationof potassium between sessions.

Additional benefits derived from frequent hemofiltration in the controlof serum potassium lay in the more physiologic control of acidosis,which prevents extra cellular shift of potassium from the intracellularspace. In addition to the control of acidosis, the avoidance of totalbody potassium depletion enhances aldosterone-mediated gut eliminationof potassium, further safeguarding against hyperkalemia.

The optimal range for chloride concentrations in a replacement fluidused for frequent hemofiltration is 105 to 115 meq/liter, and typically109 meq/liter. This concentration most closely approximates the normalsodium to chloride ratio of 1.38:1 maintained in the plasma. The smalldeviation from this ratio in the replacement fluid itself allows for thenormalization of the ratio by daily oral intake of these electrolytes.Due to the larger replacement fluid volumes needed for infrequenttreatment (three times per week or less), this deviation from the normal1.38:1 ratio are exaggerated, and can lead to a hyperchloremic acidosis.Due to the use of smaller fluid volumes during each frequenthemofiltration session, hyperchloremic acidosis can be avoided.

The optimal range of bicarbonate or an equivalent in a replacement fluidused for frequent hemofiltration is also important. Concentrations mustadequately replace filtered bicarbonate while controlling acidosis andavoiding metabolic alkalosis. Because of precipitation of calciumcarbonate in solutions containing dissolved calcium and bicarbonate,bicarbonate itself is generally impractical for use in a replacementfluid. Other substances such as acetate, citrate, or typically lactate,are substituted. These substances are metabolized by the body intobicarbonate and do not precipitate when placed into solution with thecationic substances mentioned previously.

The range of lactate necessary to replace filtered bicarbonate andcontrol acidosis without alkalemia is 25 to 35 mmoles per liter, andtypically 28 mmoles per liter. Due to the large volumes of replacementfluid used for infrequent therapies, use of lactate containingreplacement fluids can result in lactate accumulation and pathologicalterations in the lactate:pyruvate ratio and resulting in undesirablechanges in cellular redox potentials. However, these effects areminimized by the frequent use of smaller volumes of replacement fluidduring frequent hemofiltration. This also results in more physiologiccontrol of acidosis and, secondarily, serum potassium concentration. Thelatter is accounted for by reduced extra-cellular shift of potassiumcaused by acidosis.

The above observation also holds true for acetate and citrate, as well.The typical range of acetate in replacement fluid would be 25 to 35mmoles/liter, and typically 30 mmoles/liter. The typical range ofcitrate would be 16 to 24 mmoles/liter, and typically 20 mmoles/liter.These concentrations render solutions containing acetate impractical forlarge volume replacements on an infrequent basis, because of toxicityincurred by the accumulation of acetate. These include both cardiac andhepatic toxicity. There are additional issues of calcium and magnesiumchelation, which become significant when citrate is used in the largevolumes necessary for infrequent therapy. These toxic effectsattributable to acetate or citrate are minimized by the smallerreplacement volumes required for daily hemofiltration.

The unique combination of electrolytes and basic substances discussedabove represent a novel solution to the problem of choosing replacementfluid for frequent hemofiltration. The same constituents would notlikely be applicable to less frequent treatment schedules.

Frequent hemofiltration minimizes the depletion of blood electrolytesduring each hemofiltration session. Thus, the replacement fluid need notinclude replacement electrolytes. The source 252 may therefore supplyrelatively inexpensive commodity solutions of physiologic fluids, freeof electrolytes, e.g., normal saline or Ringer's lactate (whichtypically contains 6 mg/ml sodium chloride (130 meq/liter); 3.1 mg/ml ofsodium lactate (28 meq/liter); 0.3 mg/ml potassium chloride (4meq/liter); 0.2 mg/ml calcium chloride (2.7 meq/liter, 109 meq/liter atan osmolarity of 272 mos/liter); at a pH of 6.0 to 7.5). When bufferedwith citrate, Ringer's lactate effectively achieves the fluid balancingfunction. The citrate used to buffer the inexpensive, electrolyte-freereplacement fluid can also serve the additional function ofanticoagulating the blood as it undergoes hemofiltration in the firstplace.

The source 252 supplying the ancillary materials 20 can comprise one ormore companies or businesses that manufacture the ancillary materials orthat otherwise distributes the ancillary materials 20 to the treatmentlocation 12.

D. Exemplary Frequent Hemofiltration Modalities

The system 10 serves to enable frequent hemofiltration with high bloodflow rates. The high blood flow rates reduce the processing time, andalso significantly increases the transport rate of uremic toxins acrossthe hemofiltration membrane. The frequent hemofiltration that the system10 enables removes high concentrations of uremic toxins, withoutrequiring the removal of high fluid volumes, with the attendant loss ofelectrolytes. The system 10 thereby provides multiple benefits for theindividual, i.e., a tolerable procedure time (e.g., about one to twohours), with high clearance of uremic toxins, without high depletion ofliquids and physiologic electrolyte levels in the blood, accurate fluidvolume balancing, and use of inexpensive commodity replacement fluids.

The machine 16 and cartridge 18 that the system 10 may provide can beused to provide diverse frequent hemofiltration modalities on acontinuous or extended basis, e.g., normal frequent hemofiltration,balanced frequent hemofiltration, only net ultrafiltration, andreplacement fluid bolus.

During normal frequent hemofiltration, blood is drawn from the person ata prescribed flow rate (BFR). Waste fluid is removed from the arterialblood flow and volumetrically balanced with replacement fluid, which isreturned in the venous blood flow at a prescribed rate (RFR). Aprescribed net ultrafiltration volume of waste fluid is also removed ata prescribed flow rate (UFR) with fluid balancing, to control net weightloss. Operation of the machine 16 in the normal frequent hemofiltrationmode terminates when either (i) the replacement fluid sensor indicatesthe absence of replacement fluid flow by sensing the presence of air(i.e., no more replacement fluid) and the net ultrafiltration goal hasbeen achieved; or (ii) the time prescribed for the session has elapsed.

During balanced frequent hemofiltration, normal hemofiltration occurswithout an ultrafiltration function. This mode can be used for personsthat experience no weight gains between treatment sessions. This modecan also be used at the end of a normal frequent hemofiltration session,when the net ultrafiltration goal was achieved before exhausting thesupply of replacement fluid.

During only net ultrafiltration, only a net ultrafiltration volume ofwaste is removed from the person. No fluid is replaced. This mode can beused when it is desired only to remove fluid. This mode can also be usedat the end of a normal frequent hemofiltration session, when the netultrafiltration goal has not been achieved but the supply of replacementfluid has been exhausted.

During replacement fluid bolus, there is no fluid balancing andultrafiltration functions. Blood is circulated in an extracorpeal pathand a bolus of replacement fluid is added. In the illustratedembodiment, the ultrafiltration pump 144 is run in reverse at a speedlower than the waste and replacement pump 152. This recirculates wastefluid through the waste compartments 212R and 214R, to add replacementfluid from the replacement compartments 212F and 214F to the patient.The waste fluid that is recirculated limits waste fluid removal throughthe hemofilter 34, yielding replacement fluid addition withoutadditional waste fluid removal. The net volume of added replacementfluid conveyed to the patient equals the volume of waste fluidrecirculated. This mode can be used to return fluid to a person in abolus volume, e.g., during a hypotensive episode or during rinse back atthe end of a given hemofiltration session.

1. Controlling the Blood Flow Rate

High blood flow rates (e.g., at least 300 ml/min, and preferably atleast 600 ml/min) are conducive to rapid, efficient frequenthemofiltration. The high blood flow rates not only reduce the processingtime, but also significantly increases the transport rate of uremictoxins across the hemofiltration membrane. In this way, the system 10removes high concentrations of uremic toxins, without requiring theremoval of high fluid volumes, with the attendant loss of electrolytes.

The BFR can be prescribed by an attending physician and input by theoperator at the beginning of a treatment session. Alternatively, themachine 16 can automatically control to achieve an optimal BFR andminimize procedure time, based upon a desired filtration fraction value(FF), FPR, and UFR, as follows: BFR=(RFR+UFR)/FF.

where:

-   -   FF is the desired percentage of fluid to be removed from the        blood stream through the hemofilter 34.

A desired FF (typically 20% to 35%) can be either preset or prescribedby the attending physician. A desired FF takes into account the desiredtherapeutic objectives of toxin removal, as well as the performancecharacteristics of the hemofilter 34. A nominal FF can be determinedbased upon empirical and observed information drawn from a population ofindividuals undergoing hemofiltration. A maximum value of 30% isbelieved to be appropriate for most individuals and hemofilters 34, toachieve a desired therapeutic result without clogging of the hemofilter34.

In the illustrated embodiment, air leaks into the extracorporeal circuit(due, e.g., to improper patient line connection) is monitored by thesensor 98. The sensor 98 is an ultrasonic detector, which also canprovide the added capacity to sense flow rate.

In the illustrated embodiment, the machine 16 senses waste fluidpressure to control the blood flow rate to optimize the removal of fluidacross the hemofilter 34. As arterial blood flows through the hemofilter34 (controlled by the blood pump 92), a certain volume of waste fluidwill cross the membrane into the waste line 118. The volume of wastefluid entering the waste line 118 depends upon the magnitude of thewaste fluid pressure, which is sensed by the sensor 132. The waste fluidpressure is adjusted by controlling the waste fluid removal rate throughthe fluid balancing compartments (i.e., through control of the waste andreplacement pump 152).

The machine 16 monitors the waste fluid pressure at sensor 132. Bykeeping the pressure sensed by the sensor 132 slightly above zero, themachine 16 achieves the maximum removal of fluid from the blood at thenoperative arterial flow rate. Waste pressure values significantly higherthan zero will limit removal of fluid from the blood and keep a higherpercentage of waste fluid in the blood (i.e., result in a lowerfiltration fraction). However, this may be desirable for persons whotend to clot easier.

By sensing waste fluid pressure by sensor 132, the machine 16 alsoindirectly monitors arterial blood pressure. At a constant blood pumpspeed, changes in arterial blood flow caused, e.g., by access clottingor increased arterial blood pressure, makes less waste fluid availablein the waste line 118. At a given speed for pump 152, change in arterialblood flow will lower the sensed waste pressure at sensor 132 to anegative value, as fluid is now drawn across the membrane. The machine16 adjusts for the change in arterial blood flow by correcting the wastefluid removal rate through the pump 152, to bring the waste pressureback to slightly above zero, or to another set value.

In this arrangement, a pressure sensor in the arterial blood line is notrequired. If the arterial pressure increases at a fixed blood pumpspeed, the blood flow must drop, which will result in a sensed relateddrop in the waste fluid pressure by the sensor 132. Adjusting the pump152 to achieve a pressure slightly above zero corrects the reducedarterial blood flow. In this arrangement, since the waste fluid pressureis maintained at a slightly positive value, it is not possible todevelop a reverse transmembrane pressure, which conveys waste fluid backto the person's blood. The maximum transmembrane pressure is the maximumvenous pressure, since waste fluid pressure is held slightly positive.

In an alternative arrangement, arterial blood pressure can be measuredby a sensor located upstream of the blood pump. The rate of the bloodpump is set to maintain sensed arterial blood pressure at apredetermined control point. This controls the blood pump speed to amaximum rate. The control point can be determined by the attendingphysician, e.g., on a day-to-day basis, to take into account the bloodaccess function of the person undergoing treatment. Use of an arterialpressure control point minimizes the treatment time, or, alternatively,if treatment time is fixed, the removal of waste fluid can maximized.

In this arrangement, safety alarms can be included should the sensedarterial pressure become more negative than the control point, alongwith a function to shut down the blood pump should an alarm occur.

2. Controlling the Replacement Fluid Flow Rate

RFR can be prescribed by an attending physician and inputted by theoperator at the beginning of a treatment session.

Alternatively, the machine 16 can automatically control RFR to minimizeprocedure time based upon the desired filtration fraction value (FF),BFR, and UFR, as follows: RFR=(BFR*FF)−UFR.

In the illustrated embodiment, waste is conveyed to the waste sidecompartments 212R and 214R, and replacement fluid is conveyed to thereplacement side compartments 212F and 214F, by operation of the dualheader waste and replacement fluid pump 152. Alternatively, separatewaste and replacement fluid pumps can be provided.

The speed of the waste and replacement pump 152 is controlled to achievethe desired RFR. The machine 16 cycles the inlet and outlet valveassemblies 216, 218, as described. The machine 16 cycles between thevalve states according to the speed of the waste and fluid pump 152 toavoid overfilling the compartments 212, 214 receiving fluid. Varioussynchronization techniques can be used.

In one arrangement, as previously described, the interval of a valvecycle is timed according to the RFR, so that the volume of waste orreplacement fluid supplied to waste compartment during the valve cycleinterval is less than volume of the compartment receiving the wastefluid overfilling is thereby avoided without active end of cyclemonitoring. In a preferred embodiment, the waste fluid is pumped at RFR,and the replacement fluid is pumped at a higher rate, but is subject topressure relief through the pressure relief path 240 upon filling thecorresponding replacement side compartment 214.

In another arrangement, the timing of the transition between valvecycles is determined by active sensing of pressure within thecompartments 212, 214 receiving liquid. As the interior wall 210 reachesthe end of its travel, pressure will increase, signaling an end of cycleto switch valve states.

In yet another arrangement, the location of the interior wall 210 as itreaches the end of its travel is actively sensed by end of cycle sensorson the machine 16. The sensors can comprise, e.g., optical sensors,capacitance sensors, magnetic Hall effect sensors, or by radio frequency(e.g., microwave) sensors. The termination of movement of the interiorwall 210 indicates the complete filling of a compartment and theconcomitant emptying of the other compartment, marking the end of acycle. The sensors trigger an end of cycle signal to switch valvestates.

The machine 16 counts the valve cycles. Since a known volume ofreplacement fluid is expelled from a replacement side compartment duringeach valve cycle, the machine 16 can derive the total replacement volumefrom the number of valve cycles. The replacement fluid volume is alsoknown by the number of replacement fluid bags of known volume that areemptied during a given session.

Frequent hemofiltration can be conducted without fluid replacement,i.e., only net ultrafiltration, by setting RFR to zero.

3. Controlling the Ultrafiltration Flow Rate

UFR can be prescribed by an attending physician and inputted by theoperator at the beginning of a treatment session.

The speed of the ultrafiltration pump is monitored and varied tomaintain UFR.

Frequent hemofiltration can be conducted without an ultrafiltrationfunction, i.e., balanced hemofiltration, by setting UFR to zero.

4. Active Filtration Rate Control

In an alternative embodiment, the machine 16 also actively controls thefiltration rate along with the blood flow rate, to achieve a desiredmagnitude of uremic toxin removal through the hemofilter 34.

In this embodiment, the machine 16 includes a flow restrictor which ispositioned to engage a region of the venous blood return path in thecircuit 56. The restrictor comprises, e.g., a stepper-driven pressureclamp, which variably pinches a region of the venous blood return pathupon command to alter the outlet flow rate of blood. This, in turn,increases or decreases the transmembrane pressure across the filtermembrane.

For a given blood flow rate, waste transport across the filter membranewill increase with increasing transmembrane pressure, and vice versa.However, at some point, an increase in transmembrane pressure, aimed atmaximizing waste transport across the filter membrane, will drivecellular blood components against the filter membrane. Contact withcellular blood components can also clog the filter membrane pores, whichdecreases waste transport through the membrane.

Filtration rate control can also rely upon an upstream sensor mounted onthe machine 16. The sensor is positioned for association with a regionof the arterial blood supply path between the blood pump 92 and theinlet of the hemofilter 34. The sensor senses the hematocrit of theblood prior to its passage through the filter membrane which will becalled the “pre-treatment hematocrit”). In the arrangement, a downstreamsensor is also mounted on the machine 16. The sensor is positioned forassociated with a region of the venous blood return path downstream ofthe outlet of the hemofilter 34. The sensor senses the hematocrit of theblood after its passage through the hemofilter 34 (which will be calledthe “post-treatment hematocrit”).

The difference between pre-treatment and post-treatment hematocrit is afunction of the degree of waste fluid removal by the hemofilter 34. Thatis, for a given blood flow rate, the more waste fluid that is removed bythe hemofilter 34, the greater the difference will be between thepre-treatment and post-treatment hematocrits, and vice versa. Themachine 16 can therefore derive an actual blood fluid reduction ratiobased upon the difference detected by sensors between the pre-treatmentand post-treatment hematocrits. The machine 16 periodically compares thederived fluid reduction value, based upon hematocrit sensing by thesensors, with the desired FF. The machine 16 issues a command to theflow restrictor to bring the difference to zero.

5. Set Up Pressure Testing/Priming

Upon mounting the disposable fluid circuit on the machine 16, the pumpscan be operated in forward and reverse modes and the valves operatedaccordingly to establish predetermined pressure conditions within thecircuit. The sensors monitor build up of pressure within the circuit, aswell as decay in pressure over time. In this way, the machine can verifythe function and integrity of pumps, the pressure sensors, the valves,and the flow paths overall.

The machine 16 can also verify the accuracy of the ultrafiltration pumpusing the fluid balancing containers.

Priming can be accomplished at the outset of each frequenthemofiltration session to flush air and any residual fluid from thedisposable fluid circuit. Fluid paths from the arterial access to thewaste bag are flushed with replacement fluid. Replacement fluid is, alsocirculated through the fluid balancing containers into the waste bag andthe venous return path. The higher flow rate in the replacement fluidpath and timing of the fluid balancing valve elements assure that thereplacement fluid compartments completely fill and the waste fluidcompartments completely empty during each cycle for priming.

6. Rinse Back

As previously described, waste fluid pressure is controlled andmonitored to assure its value is always positive. Likewise, pressurebetween the blood pump and the hemofilter must also be positive, so thatair does not enter this region of the circuit. Forward operation of theblood pump to convey arterial blood into the hemofilter establishes thispositive pressure condition.

The rinse back of blood at the end of a given frequent hemofiltrationprocedure can also be accomplished without risk of air entry into theblood flow path. Rinse can be accomplished by stopping the blood pumpand operating the ultrafiltration pump in the reverse bolus mode, asalready described. The recirculation of waste fluid by theultrafiltration pump through the fluid balancing compartments introducesreplacement fluid to flush the venous return line. When complete, thevenous clamp is closed.

With the venous clamp closed, continued operation of the ultrafiltrationpump in the reverse bolus mode introduces replacement fluid from thefluid balancing compartments into the hemofilter, in a back flowdirection through the outlet port. The blood pump is run in reverse toconvey the replacement fluid through the hemofilter and into thearterial blood line. Residual blood is flushed from the blood line. Theblood pump is operated in reverse at a rate slower than the reversebolus rate of the ultrafiltration pump (which supplies replacement fluidto the outlet port of the hemofilter), so that air cannot enter theblood path between the blood pump and the hemofilter. At this stage ofthe rinse back, the arterial blood line is also subject to positivepressure between the blood pump and the arterial access, so no air canenter this region, either.

In this arrangement, no air sensing is required in the arterial bloodline and a pressure sensor between the blood pump and the hemofilter isrequired.

E. Supplying Telemetry

The system 10 also preferably includes a telemetry network 22 (see FIGS.1 and 19). The telemetry network 22 provides the means to link themachine 16 at the treatment location 12 in communication with one ormore remote locations 254 via, e.g., cellular networks, digitalnetworks, modem, Internet, or satellites. A given remote location 254can, for example, receive data from the machine 16 at the treatmentlocation 12 or transmit data to a data transmission/receiving device 296at the treatment location 12, or both. A main server 256 can monitoroperation of the machine 16 or therapeutic parameters of the personundergoing frequent hemofiltration. The main server 256 can also providehelpful information to the person undergoing frequent hemofiltration.The telemetry network 22 can download processing or service commands tothe data receiver/transmitter 296 at the treatment location 12.

Further details about the telemetry aspect of the system 10 will now bedescribed.

1. Remote Information Management

FIG. 19 shows the telemetry network 22 in association with a machine 16that carries out frequent hemofiltration. The telemetry network 22includes the data receiver/transmitter 296 coupled to the machine 16.The data receiver/transmitter 296 can be electrically isolated from themachine 16, if desired. The telemetry network 22 also includes a maindata base server 256 coupled to the data receiver/transmitter 296 and anarray of satellite servers 260 linked to the main data base server 256.

The data generated by the machine 16 during operation is processed bythe data receiver/transmitter 296. The data is stored, organized, andformatted for transmission to the main data base server 256. The database server 256 further processes and dispenses the information to thesatellite data base servers 260, following by pre-programmed rules,defined by job function or use of the information. Data processing tosuit the particular needs of the telemetry network 22 can be developedand modified without changing the machine 16.

The main data base server 256 can be located, e.g., at the company thatcreates or manages the system 10.

The satellite data base servers 260 can be located, for example, at theresidence of a designated remote care giver for the person, or at a fulltime remote centralized monitoring facility staffed by medically trainedpersonnel, or at a remote service provider for the machine 16, or at acompany that supplies the machine 16, or the processing cartridge 18, orthe ancillary processing material to the treatment location 12.

Linked to the telemetry network 22, the machine 16 acts as a satellite.The machine 16 performs specified therapy tasks while monitoring basicsafety functions and providing the person at the treatment location 12notice of safety alarm conditions for resolution. Otherwise, the machine16 transmits procedure data to the telemetry network 22. The telemetrynetwork 22 relieves the machine 16 from major data processing tasks andrelated complexity. It is the main data base server 256, remote from themachine 16, that controls the processing and distribution of the dataamong the telemetry network 22, including the flow of information anddata to the person undergoing therapy. The person at the treatmentlocation 12 can access data from the machine 16 through the local datereceiver/transmitter 296, which can comprise a laptop computer, handheldPC device, web tablet, or cell phone.

The machine 16 can transmit data to the receiver/transmitter 296 invarious ways, e.g., electrically, by phone lines, optical cableconnection, infrared light, or radio frequency, using cordlessphone/modem, cellular phone/modem, or cellular satellite phone/modem.The. telemetry network 22 may comprise a local, stand-alone network, orbe part of the Internet.

For example, when the machine 16 notifies the person at the treatmentlocation 12 of a safety alarm condition, the safety alarm and itsunderlying data will also be sent to the main server 256 on thetelemetry network 22 via the receiver/transmitter 296. While the personundergoing therapy or the care giver works to resolve the alarmcondition, the main server 256 determines, based upon the prevailingdata rule, whether the alarm condition is to be forwarded to otherservers 260 in the network 22.

When an alarm condition is received by the main server 256, the mainserver 256 can locate and download to the receiving device 296 theportion of the operator's manual for the machine that pertains to thealarm condition. Based upon this information, and exercising judgment,the operator/user can intervene with operation of the machine 16. Inthis way, the main server 256 can provide an automatic,context-sensitive help function to the treatment location 12. Thetelemetry network 22 obviates the need to provide on-boardcontext-sensitive help programs for each machine 16. The telemetrynetwork 22 centralizes this help function at a single location, i.e., amain server 256 coupled to all machines 16.

The telemetry network 22 can relay to an inventory server 262 supply andusage information of components used for frequent hemofiltration at eachtreatment location 12. The server 262 can maintain treatmentsite-specific inventories of such items, such as cartridges 18,replacement fluid, and hemofilters 34. The company or companies of thesystem 10 that supply the machine 16, or the processing cartridge 18, orthe ancillary processing material to the treatment location 12 can allbe readily linked through the telemetry network 22 to the inventoryserver 262. The inventory server 262 thereby centralizes inventorycontrol and planning for the entire system 10, based upon informationreceived in real time from each machine 16 at each treatment location12.

The telemetry network 22 can relay to a service server 264 hardwarestatus information for each machine 16 at every treatment location 12.The service server 264 can process the information according topreprogrammed rules, to generate diagostic reports, service requests ormaintenance schedules. The company or companies of the system 10 thatsupply or service the machine 16 can all be readily linked through thetelemetry network 22 to the service server 264. The service server 264thereby centralizes service, diagnostic, and maintenance functions forthe entire system 10. Service-related information can also be sent tothe treatment location 12 via the receiving device 296.

The telemetry network 22 can also relay to a treatment monitoring server266, treatment-specific information pertaining to the hemofiltrationtherapy provided by each machine 16 for the person at each treatmentlocation 12. Remote monitoring facilities 268, staffed by medicallytrained personnel, can be readily linked through the telemetry network22 to the treatment monitoring server 266. The monitoring server 266thereby centralizes treatment monitoring functions for all treatmentlocations 12 served by the system 10. Treatment-monitoring informationcan also be sent to the treatment location 12 via the receiving device296.

The telemetry network 22 can also provide through the device 296 anaccess portal for the person undergoing frequent hemofiltration to themyriad services and information contained on the Internet, e.g., overthe web radio and TV, video, telephone, games, financial management, taxservices, grocery ordering, prescriptions purchases, etc. The mainserver 256 can compile diagnostic, therapeutic, and/or medicalinformation to create a profile for each person served by the system 10to develop customized content for that person. The main server 256 thusprovide customized ancillary services such as on line training, billing,coaching, mentoring, and provide a virtual community whereby personsusing the system 10 can contact and communicate via the telemetrynetwork 22.

The telemetry network 22 thus provides the unique ability to remotelymonitor equipment status, via the internet, then provide information tothe user, also via the internet, at the location of the equipment. Thisinformation can includes, e.g., what page on the operator's manual wouldbe the most helpful for their current operational situation, actual dataabout the equipment's performance (e.g., could it use service, or is itset up based on the caretaker's recommendations, data about the currentsession i.e., buttons pressed, alarms, internal machine parameters,commands, measurements.

The remote site can monitor the equipment for the same reasons that theuser might. It can also retrieve information about the machine when itis turned off because the telemetry device is self-powered. It retainsall information about the machine over a period of time (much like-aflight recorder for an airplane).

2. On Site Programming

(i) Using the Telemetry Network

The main server 256 on the telemetry network 22 can also store anddownload to each machine 16 (via the device 296) the system controllogic and programs necessary to perform a desired frequenthemofiltration procedure. Programming to alter a treatment protocol tosuit the particular needs of a single person at a treatments site can bedeveloped and modified without a service call to change the machine 16at any treatment location 12, as is the current practice. System widemodifications and revisions to control logic and programs that conditiona machine 16 to perform frequent hemofiltration can be developed andimplemented without the need to retrofit each machine 16 at alltreatment locations 12 by a service call. This approach separates theimparting of control functions that are tailored to particularprocedures, which can be downloaded to the machine 16 at time of use,from imparting safety functions that are generic to all procedures,which can be integrated in the machine 16.

(ii) Using the Cartridge

Alternatively, the control logic and programs necessary to perform adesired frequent hemofiltration procedure can be carried in a machinereadable format on the cartridge 18. Scanners on the machine 16automatically transfer the control logic and programs to the machine 16in the act of loading the cartridge 18 on the machine 16. Bar code canbe used for this purpose. Touch contact or radio frequency siliconmemory devices can also be used. The machine 16 can also include localmemory, e.g., flash memory, to download and retain the code.

For example, as FIG. 2 shows, the machine 16 can include one or morecode readers 270 on the chassis panel 26. The tray 48 carries, e.g., ona label or labels, a machine readable (e.g., digital) code 272 (see FIG.10) that contains the control logic and programs necessary to perform adesired frequent hemofiltration procedure using the cartridge 18.Loading the tray 48 on the machine 16 orients the code 272 to be scannedby the reader(s) 270. Scanning the code 272 downloads the control logicand programs to memory. The machine 16 is thereby programmed on site.

The code 272 can also include the control logic and programs necessaryto monitor use of the the cartridge 18. For example, the code 272 canprovide unique identification for each cartridge 18. The machine 16registers the unique identification at the time it scans the code 272.The machine 16 transmits this cartridge 18 identification information tothe main server 256 of the telemetry network 22. The telemetry network22 is able to uniquely track cartridge 18 use by the identification codethroughout the system 10.

Furthermore, the main server 256 can include preprogrammed rules thatprohibit multiple use of a cartridge 18, or that limit extended uses toa prescribed period of time. An attempted extended use of the samecartridge 18 on any machine 16, or an attempted use beyond theprescribed time period, will be detected by the machine 16 or the mainserver 256. In this arrangement, the machine 16 is disabled until anunused cartridge 18 is loaded on the machine 16.

Service cartridges can also be provided for the machine 16. A servicecartridge carries a code that, when scanned by the reader or readers onthe chassis panel 26 and downloaded to memory, programs the machine 16to conduct a prescribed service and diagnostic protocol using theservice cartridge 18.

(iii) Using an Overlay

Alternatively, or in combination with any of the foregoing on-sitemachine 16 programming techniques, the chassis panel 26 can beconfigured to receive overlays 274, 276, 278, 280 (see FIG. 20), whichare specific to particular hemofiltration modalities or therapies thatthe machine 16 can carry out. For example, in the context of theillustrated embodiment, one overlay 274 would be specific to the normalfrequent hemofiltration mode, a second overlay 276 would be specific tothe balanced frequent hemofiltration mode, a third overlay 278 would bespecific to the only net ultrafiltration mode, and a fourth overlay 280would be specific to the replacement fluid bolus mode. Other overlayscould be provided, e.g., for a pediatric hemofiltration procedure, or aneo-natal hemofiltration procedure.

When a treatment location 12 wants to conduct a particularhemofiltration modality, the treatment location 12 mounts the associatedoverlay on the chassis panel 26. Each overlay contains a code 282 or achip imbedded in the overlay that is scanned or discerned by one or morereaders 284 on the chassis panel 26 after the overlay is mounted on thechassis panel 26. The code 282 is downloaded to flash memory on themachine 16 and programs the machine 16 to conduct hemofiltration in thatparticular mode.

A person at the treatment location 12 mounts the appropriate overlay274, 276, 278, 280 and then mounts a cartridge 18 on the chassis panel26. The machine 16 is then conditioned by the overlay and made capableby the cartridge 18 to conduct that particular mode of hemofiltrationusing the cartridge 18. In this way, a universal cartridge 18, capableof performing several hemofiltration modes, can be provided. It is theoverlay that conditions the machine 16 to perform different treatmentmodalities. Alternatively, the operator can link the overlay, machine,and cartridge together by therapy type.

Furthermore, treatment-site specific alterations of generichemofiltration modes can be developed and implemented. In thisarrangement, treatment-site specific overlays 286 are provided for themachine 16. The treatment site-specific overlay 286 carries a code 282or a chip imbedded in the overlay that, when downloaded by the machine16, implements a particular variation of the hemofiltration mode for theperson at that treatment location 12, as developed, e.g., by anattending physician. A person at the treatment location 12 mounts thetreatment-site specific overlay 286 and then mounts a universalcartridge 18 on the chassis panel 26. The machine 16 is conditioned bythe treatment site-specific overlay 286 and made capable by theuniversal cartridge 18 to conduct that particular specific mode ofhemofiltration using the cartridge 18.

An additional overlay 288 can be provided that contains code 282 or achip imbedded in the overlay that, when scanned by the reader(s) 284 onthe chassis panel 26 and downloaded to flash memory, programs themachine 16 to conduct a prescribed service and diagnostic protocol usingthe cartridge 18, which is also mounted on the chassis panel 26.

F. Extended Use of the Cartridge

The consolidation of all blood and fluid flow paths in a single, easilyinstalled cartridge 18 avoids the potential of contamination, byminimizing the number of connections and disconnections needed during ahemofiltration session. By enabling a dwell or wait mode on the machine16, the cartridge 18 can remain mounted to the machine 16 after onehemofiltration session for an extended dwell or break period and allowreconnection and continued use by the same person in a subsequentsession or in a continuation of a session following x-rays or testing.

The cartridge 18 can therefore provide multiple intermittent treatmentsessions during a prescribed time period, without exchange of thecartridge 18 after each treatment session. The time of use confines aretypically prescribed by the attending physician or technical staff forthe treatment center to avoid biocontamination and can range, e.g., from48 hours to 120 hours, and more typically 72 to 80 hours. The cartridge18 can carry a bacteriostatic agent that can be returned to the patient(e.g., an anticoagulant, saline, ringers lactate, or alcohol) and/or berefrigerated during storage.

To reduce the change of biocontamination, the cartridge 18 can includeone or more in-line sterilizing filters 178 (e.g., 0.2 m) in associationwith connectors that, in use, are attached to outside fluid sources,e.g., the replacement fluid source. As FIG. 11 shows, the filter 178 canbe pre-attached to the cartridge 18 and be coupled to a multipleconnection set 290, which itself is coupled to the prescribed number ofreplacement fluid bags 176. Alternative (as FIG. 21 shows), a separatecustomized filtration set 292 can be provided, which attaches to theconnector 174 carried by the cartridge 18. The filtration set 292includes a sterilizing filter 178 to which an array of multipleconnector leads 294 is integrated.

In the dwell mode of the machine 16, fluid can be recirculated eithercontinuously or intermittently through the circuit 56. The fluid can becirculate past a region of ultraviolet light carried on the machine 16to provide a bacteriostatic effect. Alternatively, or in combinationwith exposure to ultraviolet light, the fluid can carry a bacteriostaticagent, such as an anticoagulant, saline, ringers lactate, or alcohol,which can be returned to the person at the beginning of the nexttreatment session. The machine 16 and cartridge 18 can also be subjectedto refrigeration during the dwell period.

In an alternative embodiment, an active disinfecting agent can becirculated through the circuit 56 during the dwell period.The-disinfecting material can include a solution containing AmuchinaJmaterial. This material can be de-activated by exposure to ultravioletlight prior to the next treatment session. Exposure to ultraviolet lightcauses a chemical reaction, during which AmuchinaJ material breaks downand transforms into a normal saline solution, which can be returned tothe person at the start of the next hemofiltration session.

G. The Operator Interface

FIG. 22 shows a representative display 324 for an operator interface 44for the machine. The display 324 comprises a graphical user interface(GUI), which, in the illustrated embodiment, is displayed by theinterface 44 on the exterior of the door 28, as FIG. 2 shows. The GUIcan be realized, e.g., as a membrane switch panel, using an icon-basedtouch button membrane. The GUI can also be realized as a “C” languageprogram implemented using the MS WINDOWS™ application and the standardWINDOWS 32 API controls, e.g., as provided by the WINDOWS™ DevelopmentKit, along with conventional graphics software disclosed in publicliterature.

The GUI 324 presents to the operator a simplified information input andoutput platform, with graphical icons, push buttons, and display bars.The icons, push buttons, and display bars are preferably back-lighted ina purposeful sequence to intuitively lead the operator through set up,execution, and completion of a frequent hemofiltration session.

The GUI 324 includes an array of icon-based touch button controls 326,328, 330, and 332. The controls include an icon-based treatmentstart/select touch button 326, an icon-based treatment stop touch button328, and an icon-based audio alarm mute touch button 330. The controlsalso include an icon-based add fluid touch button 332 (for prime, rinseback, and bolus modes, earlier described).

An array of three numeric entry and display fields appear between theicon-based touch buttons. The fields comprise information display bars334, 336, and 338, each with associated touch keys 340 to incrementallychange the displayed information. In the illustrated embodiment, the topdata display bar 334 numerically displays the Replacement Fluid FlowRate (in ml/min), which is the flow rate for removing waste fluid andreplacing it with an equal volume of replacement fluid. The middle datadisplay bar 336 numerically displays the ultrafiltration flow rate (inkg/hr), which is the flow rate for removing waste fluid to control netweight loss. The bottom data display bar 338 numerically displays theBlood Pump Flow Rate (in ml/min).

The associated touch keys 340 point up (to increase the displayed value)or down (to decrease the displayed value), to intuitively indicate theirfunction. The display bars 334, 336, and 338 and touch keys 340 can beshaded in different colors, e.g., dark blue for the replacement flowrate, light blue for ultrafiltrational flow rate, and red for the bloodflow rate.

An array of status indicator bars appears across the top of the screen.The left bar 342, when lighted, displays a “safe” color (e.g., green) toindicate a safe operation condition. The middle bar 344, when lighted,displays a “cautionary” color (e.g., yellow) to indicate a caution orwarning condition and may, if desired, display a numeric or letteridentifying the condition.

The right bar 346, when lighted, displays an “alarm” color (e.g., red)to indicate a safety alarm condition and may, if desired, display anumeric or letter identifying the condition.

Also present on the display is a processing status touch button 348. Thebutton 348, when touched, changes for a period of time (e.g., 5 seconds)the values displayed in the information display bars 334, 336, and 338,to show the corresponding current real time values of the replacementfluid volume exchanged (in the top display bar 334), the ultrafiltratevolume (in the middle display bar 336), and the blood volume processed(in the bottom display bar 338). The status button 348, when touched,also shows the elapsed procedure time in the left status indicator bar342.

The display also includes a cartridge status icon 350. The icon 350,when lighted, indicates that the cartridge 18 can be installed orremoved from the machine 16.

The GUI 324, though straightforward and simplified, enables the operatorto set the processing parameters for a given treatment session indifferent ways.

For example, in one input mode, the GUI 324 prompts the operator byback-lighting the replacement fluid display bar 334, the ultrafiltrationdisplay bar 336, and the blood flow rate display bar 338. The operatorfollows the lights and enters the desired processing values using theassociated touch up/down bottons 340. The GUI back-lights thestart/select touch button 326, prompting the operator to begin thetreatment. In this mode, the machine 16 controls the pumps to achievethe desired replacement fluid, ultrafiltration, and blood flow rates setby the operator. The machine terminates the procedure when all thereplacement fluid is used and the net ultrafiltration goal is achieved.

In another input mode, the operator can specify individual processingobjectives, and the machine 16 will automatically set and maintainappropriate pump values to achieve these objectives. This mode can beactivated, e.g., by pressing the start/select touch button 326 whilepowering on the machine 16. The GUI 324 changes the. function of thedisplay bars 334 and 336, so that the operator can select and changeprocessing parameters. In the illustrated embodiment, the processingparameters are assigned identification numbers, which can be scrolledthrough and selected for display in the top bar 334 using the touchup/down keys 340. The current value for the selected parameter isdisplayed in the middle display bar 336, which the operator can changeusing the touch up/down keys 340.

In this way, the operator can, e.g., specify a desired filtration factorvalue (FF) along with a desired ultrafiltration flow rate (UFR) andreplacement fluid flow rate (RFR). The machine will automaticallycontrol the blood pump rate (BFR), based upon the relationshipBFR=(RFR+UFR)/FF, as previously described.

Alternatively, the operator can specify a desired filtration factorvalue (FF) along with a desired ultrafiltration flow rate (UFR) andblood flow rate (BFR). The machine will automatically control thereplacement fluid pump rate (RFR), based upon the relationshipRFR=(BFR*FF)−UFR, as already described.

Alternatively, the operator can specify only an ultrafiltration volume.In this arrangement, the machine 16 senses waste fluid pressure toautomatically control the blood flow rate to optimize the removal offluid across the hemofilter 34, as previously described. Alternatively,the machine can automatically control the blood flow rate to optimizeremoval of fluid based a set control arterial blood pressure, as alsoalready described.

As FIG. 22 shows, the interface also preferably includes an infraredport 360 to support the telemetry function, as previously described.

As FIG. 23 shows, the interface 44 can include a generic display panel352 that receives a family of templates 354. Each template 354 containscode 356 or chip that, when scanned or discerned by a reader 358 on theinterface panel 352, programs the look and feel of the interface 44. Inthis way, a generic display panel 352 can serve to support a host ofdifferent interfaces, each optimized for a particular treatmentmodality.

Various features of the invention are set forth in the following claims.

1. A renal replacement therapy system comprising an extracorporeal circuit for circulating blood from an individual through a blood treatment device to remove waste, the extracorporeal circuit including a blood line coupled to the blood treatment device and adapted to draw blood from the individual, a blood pump to convey blood through the blood line from the individual into the blood treatment device at a blood flow rate, a waste removal line to convey waste fluid from the blood treatment device, a sensor in the blood line to sense blood pressure, and a controller coupled to the sensor and the blood pump to adjust the blood flow rate to maintain blood pressure at a predetermined set value.
 2. A system according to claim 1 wherein the controller generates an alarm output based upon variance between sensed blood pressure and the predetermined set value.
 3. A system according to claim 2 wherein the alarm output terminates operation of the blood pump.
 4. A method for carrying out renal replacement therapy comprising the steps of conveying blood from the individual at a blood flow rate through a blood line into a blood treatment device to remove waste fluid, conveying waste fluid from the blood treatment device through a waste removal line, sensing blood pressure in the blood line, and adjusting the blood flow rate to maintain blood pressure at a predetermined set value.
 5. A method according to claim 4 further including the step of generating an alarm output based upon variance between sensed blood pressure and the predetermined set value.
 6. A method according to claim 5 wherein the alarm output terminates operation of the blood pump.
 7. A renal replacement therapy system, comprising: a filter; an arterial blood line connectable to a patient access and adapted to convey blood from said patient access to a filter; a venous blood line connectable to said patient access and adapted to convey blood from said filter to patient access; and a pump configured to convey blood through said arterial blood line, a sensor to sense pressure in said arterial blood line, and a controller connected to receive a pressure signal from said sensor and to control a rate of flow of said pump; said controller being configured to maintain a constant pressure in said arterial blood line by regulating a speed of said pump in response to said pressure signal.
 8. A system as in claim 7, wherein said controller is configured to slow said rate of flow when said pressure drops.
 9. A system as in claim 8, wherein said controller is configured to speed up said rate of flow when said pressure increases.
 10. A system as in claim 7, wherein said controller is configured to control said rate of flow by controlling a speed of said pump.
 11. A system as in claim 7, wherein said controller is a microcomputer programmed to compare said pressure signal with a predetermined value.
 12. A system as in claim 7, wherein said controller is configured such that when said patient access becomes clogged, said rate of flow is slowed. 